Ume University

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Medical Biobank
Umeå University
Sweden
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Northern Sweden Health and Disease Study

• Population based cohorts Questionnaires and
  blood sampling occasions

Number The Västerbotten Project Cohort 1985
- 82 000
The Northern Sweden Monica Cohort
13 000 from 1986,
1990, 1994, 1999 ( follow up), 2004
( 4 500)
The Västerbotten Mammary Screening Cohort 1995
- 47 000
Unique individuals
85 000
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Possibilities and problems of conducting long
term cancer epidemiology based on biobanks
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? Some experiences from the NSHDS ? Statements
on how to promote science
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Surprises in prostate cancer research?Risk
factors with an unexpected behaviour

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WHO BIENNIAL REPORT 2001-2002, IARC, France 2001.
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Table 1. Relative risk of cancer according to
plasma glucose levels in the Northern Sweden
Health and Disease cohort
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Table 4. Odds ratios of prostate cancer by
quintiles of serum levels of free testosterone
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• Conclusion prostate cancer
• ? It is evident that the story of surprises will
  continue.
• ? We will always be confused on a higher level.
• ? That is also called scientific development.

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Experiences in colorectal cancer research?Risk
factors which are difficult to communicate

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WHO BIENNIAL REPORT 2001-2002, IARC, France 2001.
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Meat, Fish, and Colorectal Cancer Risk The
European Prospective Investigation into Cancer
and Nutrition Teresa Norat, Sheila Bingham,
Pietro Ferrari, Nadia Slimani, Mazda Jenab,
Mathieu Mazuir, Kim Overvad, Anja Olsen, Anne
Tjønneland, Francoise Clavel, Marie-Christine
Boutron-Ruault, Emmanuelle Kesse, Heiner Boeing,
Manuela M. Bergmann, Alexandra Nieters, Jakob
Linseisen, Antonia Trichopoulou, Dimitrios
Trichopoulos, Yannis Tountas, Franco Berrino,
Domenico Palli, Salvatore Panico, Rosario Tumino,
Paolo Vineis, H. Bas Bueno-de-Mesquita, Petra H.
M. Peeters, Dagrun Engeset, Eiliv Lund, Guri
Skeie, Eva Ardanaz, Carlos González, Carmen
Navarro, J. Ramón Quirós, María-José Sanchez,
Göran Berglund, Irene Mattisson, Göran Hallmans,
Richard Palmqvist, Nicholas E. Day, Kay-Tee Khaw,
Timothy J. Key, Miguel San Joaquin, Bertrand
Hémon, Rodolfo Saracci, Rudolf Kaaks, Elio
Riboli Journal of the National Cancer
Institute, Vol. 97, No. 12, 906-916, 2005
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Norat T et al, JNCI 200597906-916.
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Hazard ratios (HRs) per 100-g increase in intake
and 95 confi dence intervals (CIs) were
calculated for calibrated intakes of fish
Norat T et al, JNCI 200597906-916.
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Red and processed meat increases risk of
colorectal cancer particularly in people who eat
little lt 17 g fibre
Fibre
Meat
(gt17, 28, lt28g fibre. Interaction p 0.06 Norat
et al, JNCI 2005, submitted)
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Meat Consumption and Risk of Colorectal Cancer ?
Higher risk of distal colon cancer associated
with processed meat (RR, 1.50 95 confidence
interval CI, 1.04-2.17), ? High consumption of
red meat reported in 1992/1993 was associated
with higher risk of rectal cancer (RR, 1.71 95
CI, 1.15-2.52 P.007 for trend), ? Long term
consumption of poultry and fish was inversely
associated with risk of both proximal and distal
colon cancer.
Chao A et al. JAMA
2005293172-182.
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Larsson et al. Int J Cancer 2005113829-834.
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World Cancer Research Fund American Institute
for Cancer Research Food Nutrition and the
Prevention of Cancer a global perspective. 1997,
pp 30.
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Japanese National Nutritional Survey during
the last 50 years Increase intake of
? milk 20-fold ? meat 9-fold ?
eggs 7-fold ? animal fat and vegetable oil
6-fold ? fruit 3-fold. Kuriki K et al.
Nutr Cancer 20055170-177.
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World Cancer Research Fund American Institute
for Cancer Research Food Nutrition and the
Prevention of Cancer a global perspective. 1997,
pp 50.
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Conclusion ? The results on meat and colorectal
cancer are stongly supported!

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A seminar with journalists 20 years ago How
will you help us to spread our messages?
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SÖNDAG 3 JULI 2005 DN.
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SÖNDAG 3 JULI 2005 DN.
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SÖNDAG 3 JULI 2005 DN.
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At the end of the story Eat, drink and be happy.
The only real threats are smoking, to much
alcohol, to much sun exposure, overweight and
physical inactivity.
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Conclusions from Focus DN,
SUNDAY 3 JULY 2005 1 ? The article was
generally received very well ? All information
was correct ? Are the conclusions of the
consumers correct? ? What is the effect of the
message on meat and HRT? ? Do the consumers care
any longer?
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What are the roles of scientists and
journalists? ? To present valid information! ?
Marketing of their messages! ? Difficult to do
with limited space!
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The challenge for both are to reach the consumers
with a correct message they ? Understand and
believe ? Not get offended by
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Genetic studies give further support!
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Interaction between family history of colorectal
cancer in first-degree relatives and health and
lifestyle factors and risk of colorectal
cancer ___________________________________________
____________________
No Family History Yes Family History p Value p
Value OR (95 CI)a
OR (95 CI) additive
multiplicative ___________________________________
____________________________ Western diet
Low 1.00
1.24 (0.801.92) 0.02 0.03
Intermediate 1.15 (0.981.35) 1.82
(1.402.36) High 1.45
(1.181.77) 3.59 (2.295.62) ___________________
____________________________________________ a
All variables in logisitic models along with
study, age, sex except for sigmoidoscopy
screening and HRT. Sigmoidoscopy screening
excluded from model because of 124 cases and 195
controls missing data.

Adopted fromm Slattery ML et al. Cancer
cause contrl 200314884.
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Sachse C et al. Carcinogenisis 2002231839-1849.
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Dietary advise based on genetics vision for the
future
Blood samples
Computerized risk assessment
Dietary advice
Genotyping
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Welcome to the NuGO Weblog The Nutrigenomics
Organisation is carried by scientists. This
weblog is the place were they speak out loud
about their passion NutriGenomics.
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Studies using specific biomarkers a possibility
for the future!
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Red meat and colorectal cancer
Adopted from Amanda J et al. Env Molec Mutag
20044444-45
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The position of the scientists
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How do scientists succeed in biobank research??

• ? Interest and knowledge
• ? Motivation and provocation
• ? Energy and devotion
• ? Skill and smartness
• ? Decades (?) of work and sacrifice

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Highlights of Medical Biobank Research
Etiology of cancer (HPV) Serology and
tissue-PCR Early diagnosis and prevention of
disease
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The position of the scientists must be protected!
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General management of a biobank
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Procedures for project evaluation
? Approval by the Boards of Experts
? Approval by the Research Ethics Committee
? Approval by the Medical Biobank
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Quality Control

• ? A system for quality control must cover all
  ...activities in the biobank, some main points
• Ownership, legal issues
• Logistics and sample handling
• Ethics, security

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Statement by the Joint Steering Committee of the
Medical Biobank

• There are two major parties involved in
  signing the contracts in a university, the
  scientists and the funding organisations .
• Both the university and the scientists have a
  legal responsibility.

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------ that the principal investigators in each
country have legal responsibilities for the
proper custody and use of both biological samples
and data from their cohort, wherever
held,------
Statement of the EPIC Steering Committee

15 October 2003
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END
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SÖNDAG 3 JULI 2005 DN.
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SÖNDAG 3 JULI 2005 DN.
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Colorectal cancer risk associated with family
history of colorectal cancer can be reduced
through having ? screening sigmoidoscopies, ?
eating a healthy diet, ? not smoking cigarettes,
? and maintaining a BMI below 25.
Slattery ML et al. Cancer cause contrl
200314879-887.
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The European Nutrigenomics Organisation
 linking genomics, nutrition and health research
(NuGO)
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Nnutrients and gene expression
Diet
                                      
Nutrients
Metabolism
Genexpression
Phenotype variation
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Genetiska associations studier
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Nutritional genomics, or nutrigenomics ?
Interaction of the genome with its nutritional
environment. ? Determine what foods and
nutrients and how much an individual should eat
to maintain an optimal health.
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EARLY DIAGNOSIS What precedes development of
RA? Klareskog, Alfredsson, Rantapää et al.
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• Combined autoantibodies to cyclic citrullinated
  peptide (CCP) and HLA-DRB1 locus antigens is
  strongly associated
• with future onset of rheumatoid arthritis.
• ? OR 66.8, 95 CI 8.3-539.4 in predicting RA
• ? Only anti-CCP ab OR 25.01, 95 CI
  2.8-222.2
• .
• Berglin E et al. Arthritis Res Ther
  20046(4)R303-R308.

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Rheumatoid arthritis

• ? Low prevalence in Mediterranean countries
• ? Cretan diet reduces disease activity
• Linda Hagfors, Thesis Umeå University
  2003

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Vision Rheumatoid arthritisTreatment before
clinical symtoms??

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The final Statement of the Research Ethics
Committee, Dec. 2003

• ? The Medical Biobank should have a principle
  investigator.
• ? The Declaration of Helsinki should be followed
  by the Medical Biobank.
• ? 9, 15 and 22 in the Declaration of Helsinki
  have not been followed by the authorities.

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The Declaration of Helsinki   approval to a
specially appointed ethical review committee,
which must be independent of the investigator,
the sponsor or any other kind of undue
influence. The researcher should also submit to
the committee, for review, information regarding
funding, sponsors, institutional affiliations,
other potential conflicts of interest and
incentives for subjects.   Conclusion The
statement is clear, the scientist is submitting
the ethical application and has the
responsibility.
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The Declaration of Nürnberg   The declaration of
Nürnberg is regarded as the basic document for
ethics of research in humans.   The duty and
responsibility for ascertaining the quality of
the consent rests upon each individual who
initiates, directs or engages in the experiment.
It is a personal duty and responsibility which
may not be delegated to another with
impunity.   Conclusion A principle investigator
is not allowed to transfer the legal and moral
responsibility to the authorities.
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Hilary Rose, Nature 2003 204 123-124.
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Heavey PM et al. Nutr Cancer 200448124-141.
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Heavey PM et al. Nutr Cancer 200448124-141.
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Nutrigenomics ? Pharmacogenomics has led to the
concept of personalized medicine. Nutrigenomics
open the way for personalized nutrition. ?
Nutrigenomics should enable individuals to manage
better their health by matching their diets with
their unique genetic makeup. ? Relevant for the
whole population or for specific groups?
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Highlights of Medical Biobank Research
Etiology of diseases (e.g. HPV)
Identification of new risk factors/indicators
Early diagnosis of diseases
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Hormones, gene polymorphisms cancer risk (2)
NCI Breast Prostate Cohort Consortium Project
on Hormones and Gene Variants
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MIGRANT STUDIES Migration studies proves beyond
reasonable doubt that genetic factors can not be
primarily responsible for the large difference in
cancer rates in different regions and countries.
World Cancer Research Fund American Institute
for Cancer Research Food Nutrition and the
Prevention of Cancer a global perspective. 1997.
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Statement by the Joint Steering Committee of the
Medical Biobank

• In Swedish universities the authorities are
  expected to decide if they can accept that the
  university can receive the contract and to check
  that the contracts are followed by the
  scientists.

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Statement by the Joint Steering Committee of the
Medical Biobank

• The scientists also have a legal responsibility
  for their actions and contracts. If contracts are
  to be changed they must be re-negotiated (a
  statement also made by the Medical biobank
  auditor).

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World Cancer Research Fund American Institute
for Cancer Research Food Nutrition and the
Prevention of Cancer a global perspective. 1997,
pp 32.
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